DESCRIPTION (From the Applicant's Abstract): Proper development of the eye involves a series of complex interactions between different tissues in the developing embryo. Although these processes have been the subject of many elegant studies for nearly a century, various tools which have been developed and refined within recent years now allow the exploration of these interactions in mammalian eye development with unprecedented precision. The appropriate development of the eye undoubtedly involves the expression of a precise combination of genes at the correct time and place within the developing embryo. The important roles of the transcription factors such Pax6 in eye development have been extensively studied in the past. The role of another transcription factor Gli-3, in mouse eye development is the subject of this research proposal. The important role of Gli-3 in aspects of development is reflected in the severe abnormal phenotypes in both mice and humans with mutations in the Gli-3 gene. Mutation in the Gli-3 gene in humans results in the disorder Greig cephalopolysyndactyly (GCPS), characterized by post-axial ad pre-axial polydactyly, syndactyly of hands and feet and craniofacial and eye abnormalities. Mice with mutations in the Gli-3 gene (Xt/Xt mice) are an animal model for GCPS and display multiple brain and eye defects pin addition to well-characterized limb defects. This research proposal aims to study the expression patterns of potential downstream targets of Gli-3 and proposes to use chimeric mice as a tool to elucidate Gli-3's function in mouse eye development.